tbuckley/cabot-search huggingface dataset:
Open-labeled placebo for the treatment of cancer-related-fatigue in patients with advanced cancer: Results of a randomized controlled trial.
Authors: Sriram Yennu, Ahsan Azhar, Zhanni Lu, Ashley Rodriguez, Adrienne Arechiga, Maria Guerra-Sanchez, Penny A Stanton, Clark Andersen, Diana L. Urbauer, Eduardo Bruera
Journal: Journal of Clinical Oncology (2022)

12006 Background: Despite the high frequency of cancer related fatigue (CRF) in patients with advanced cancer (PAdC), there are no effective pharmacological treatments. Our group previously found that the placebo response was 56% among PAdC participating in CRF trials. There are no clinical trials using open label placebo for CRF in PAdC. The purpose of this study was to determine the effects of open labeled placebo (OLP) compared to waitlist control (WLC) in reducing CRF in PAdC using Functional Assessment of Chronic Illness Therapy-Fatigue subscale (FACIT-F). Methods: In this randomized controlled trial, PAdC with fatigue ≥ 4/10 on ESAS were randomized to OLP one tablet twice a day or WLC for seven days (primary end point). After week 1 in patients of both arms received placebo for 3 weeks. Changes in FACIT-F from baseline to Day 8 (primary outcome), and changes after 21 days of placebo in both arms were assessed. Secondary outcomes included quality of life (QOL)[FACT-G], fatigue dimensions(MFSI-SF), depression(CES-D), and Fatigue cluster(ESAS fatigue, pain, and depression). Results: 82/90(91%) patients were evaluable. The adherence to placebo [mean%(SD)], was 93.6(18.6), and 88.1(20.2) at Day 8 and Day 29 respectively in OLP arm, and 89.9 (73) at Day 29 in WLC arm. The mean(SD) FACIT-F change at day 8 was 6.6 (7.6) after OLP, 2.1 (9.4) after WLC (p = 0.016). On days 15 and 29, when all patients received OLP, there was significant improvement of CRF but not difference between arms. FACT-G Total Score, FACT-G EWB, ESAS Fatigue, and Fatigue cluster score, all showed significant evidence of reduced CRF in the OLP arm on Day 8 of the study (p = 0.002, 0.030, 0.029, and 0.044, respectively). There was no significant difference in adverse events between the two groups. Conclusions: Open labeled placebo was efficacious in reducing CRF, fatigue cluster, and QOL in fatigued advanced cancer patients at the end of one week. The improvement in fatigue was maintained for 4 weeks. Further studies of this intervention are justified. Clinical trial information: NCT03927885.
The association between minimal residual disease status and survival outcomes in transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM) patients: Systematic review.
Authors: Zunairah Shah, Israr Khan, Insija Ilyas Selene, Syed Hamza Bin Waqar, Razwana Khanam, Qurrat-ul-ain Abid, Nayha Tahir, Sanjivani Sathe, Babray Laek, Asmi Chattaraj, Zinath Roksana, Irisha Badu, Faiz Anwer
Journal: Journal of Clinical Oncology (2022)

e20009 Background: Despite expanding therapeutic armamentarium of multiple myeloma (MM), it remains an incurable disease. Therefore, there is a need to assess the impact of deeper hematological responses to better gauge treatments in clinical trials and routine practice. The presence of minimal residual disease (MRD), is becoming crucial and a new standard in monitoring remission status. Clinical evidence shows that MRD status after treatment is an independent prognostic factor for MM. This review summarizes current data on MRD status and its role in predicting progression-free survival (PFS) and overall survival (OS) outcomes. Methods: We performed a literature search on four databases (PubMed, Embase, Cochrane, and Web of Science) following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. We screened 1307 studies using the Mesh terms “Multiple Myeloma and Minimal Residual disease.” After excluding review, duplicate, and non-relevant articles, 7 studies were included. Results: The association between MRD status and outcomes, including survival in TIE-NDMM patients was assessed in 7 studies, including 1083 patients. MRD status was determined using different techniques, such as flow cytometry and clonoSEQ. Different regimens were used in all studies. PFS was reported in all studies. Compared with MRD positive status, achieving MRD negativity improved PFS to 58 months versus 28.65 months as per cumulative analysis. The cumulative OS reported in 2 studies (n=196) was 95.85% in MRD-negative patients compared to 55.65% in MRD positive patients. Conclusions: Further clinical data focusing on post-treatment assessment of MRD will be useful in clinical decision-making and could be practice changing. MRD status may serve as surrogate end-points for PFS and OS in ongoing and future clinical trials. Achieving durable MRD negativity with PFS improvement might also increase the time between treatment relapses for MM and might help switch to a lesser aggressive regimen, chemotherapy-free period, avoiding drug toxicity. [Table: see text]
Diagnosis of asymptomatic bone metastases from breast cancer.
Authors: Julia N. Krokhmal, Lyudmila Ya Rozenko, Elena M. Frantsiyants, Nailya K. Guskova, Marina A. Gusareva, Marina I. Vereskunova, Ekaterina A. Guskova, Irina A. Udalenkova, Aliya K. Donskaya, Olesya N. Selyutina, Anna A. Solntseva, Ekaterina O. Vasilieva, Ekaterina A. Tolmacheva, Elena A. Karnaukhova, Olga G. Rodionova, Iuliana S. Shatova, Larisa N. Vashchenko, Tatiana V. Ausheva, Vitaliy I. Voshedskiy, Pavel G. Sakun
Journal: Journal of Clinical Oncology (2022)

e13042 Background: The purpose of this study was to analyze the prognostic value of blood levels of fibrinogen (F) in bone metastases from breast cancer (BC). Methods: The study included 160 patients with nodular BC pT2-3N0-1M0-1, including 48 patients in a prospective group (PG) and 112 patients in a retrospective group (RG). All patients underwent initial clinical and laboratory examinations, including determination of alkaline phosphatase (AP) activity (Cobas Integra 4000 plus, Switzerland) and parameters of coagulation hemostasis (STA Compact, France). Bone scintigraphy was performed for complaints of bone pain and/or in cases of elevated AP activity, regardless of SXCT data. Results were considered statistically significant at p &lt; 0.05. Results: Patients in PG were divided into two subgroups depending on F levels: in 31 (64.6%) patients F = 3.67±0.5 g/L, insignificantly exceeding the norm (2.8±0.3 g/L); in 17 (35.4%) patients F = 6.9±0.3 g/L, being 1.9 and 2.5 times (p &lt; 0.05) higher than in subgroup 1 and the norm, respectively. AP activity exceeded the norm by 26% and 40%, respectively (p &lt; 0.1). Bone metastases were detected before treatment in 24 (21.4%) women of RG with pain syndrome; all these patients showed increased blood levels of F, on average up to 7.86±0.8 g/L, similarly to patients in subgroup 2 of PG. F levels in other 88 (78.6%) patients in RG were 3.4±0.6 g/L. The nature and severity of AP changes in RG patients and in both PG subgroups were similar. Initially elevated F levels in 17 PG patients remained unchanged after antitumor treatment (6.2±0.6 g/L). AP activity values were stable after treatment being only 36% and 28% (p &lt; 0.1) higher than the norm, respectively. None of the patients with high F levels complained about bone pain. Unscheduled bone scintigraphy was appointed to 17 patients of PG without clinical symptoms or x-ray (SXCT) signs of pathology but with initially high F which did not decline after treatment. Bone scintigraphy showed metastases to the spine and pelvic bones in 12 of 17 (70.5%) patients 1 month after treatment, subsequently confirmed by MRI results. Conclusions: Initial levels of F within 6.9±0.6 g/L which do not decline after the special treatment allow predicting unfavorable BC course and the presence of metastases to the spine and/or pelvic bones without clinical signs of progression. The proposed method allows diagnosis of advanced tumor process in the absence of clinical signs of the disease with an accuracy of 87.8%, and allows timely corrections to the treatment plan.
Prediction of peritoneal cancer index and prognosis in peritoneal metastasis of gastric cancer using NLR-PLR-DDI score.
Authors: Zhihui Jiang, Yu Pengfei, Pingyuan Yu, Yang Cao, Zeyao Ye, Tengjiao Chai, Yian Du
Journal: Journal of Clinical Oncology (2022)

e16022 Background: Peritoneal metastasis is the most common metastatic mode of advanced gastric cancer, which is prone to poor prognosis and is also one of the common causes of death in patients with distant gastric cancer metastasis.The purpose of this paper was to establish a new hematologic scoring (an NPD scoring) by the neutrophil-lymphocyte ratio (NLR) and platelet- lymphocyte ratio (PLR) A and D-dimer (DDI), and its association with the peritoneal cancer index (PCI) was evaluated, and the ability of NPD scoring system to judge the prognosis of peritoneal metastasis of gastric cancer. Methods: This was a single-center, nonrandomized, retrospective, cohort study.102 patients with peritoneal metastasis of gastric cancer who underwent diagnostic staging laparoscopy (DSL) were enrolled and assessed with PCI scores.. According to the first PCI (PCI &lt; 15), the patients were divided into low PCI group (n = 67) and high PCI group (n = 35). Through univariate analysis and multivariate analysis, it was found that NLR, PLR and DDI were related to high PCI (≥ 15), and NPD scoring system was established. Chi-square test was used to evaluate the relationship between NPD score, PCI and prognosis. Results: The cohort study found that the differences of NLR, PLR and DDI between low PCI group (n = 67) and high PCI group (n = 35) were statistically significant (P &lt; 0.05). Univariate and multivariate analysis showed that NLR, PLR and DDI were independent risk factors for high PCI (P &lt; 0.05). The NPD score of patients in the high PCI group was significantly higher than those in the low PCI group (P = 0.001). The survival rate of patients in high-risk group (NPD ≥ 2 points) was significantly lower than that in low-risk group (NPD &lt; 2 points) (P = 0.003). Multivariate analysis showed that PCI and NPD score ≥ - 2 were independent predictors of OS. Conclusions: NPD score can be used as a blood marker to predict PCI and prognosis in patients with peritoneal metastasis of gastric cancer, and to guide clinical treatment. This new scoring system is an economic and convenient tool for predicting PCI and judge the prognosis of peritoneal metastasis.
Discovery and clinical validation of cost-effective noninvasive early detection of hepatocellular carcinoma (HCC) through circulating tumor DNA (ctDNA) methylation signature.
Authors: Xin-Rong Yang, Rui Liu, Jian Zhou, Jia Fan, De-Zhen Guo, Ao Huang, Yingchao Wang, Zhixiong Cai, Hui Wang, Qichang Yang, Zhixi Su, Chengcheng Ma, Minjie Xu, Wei Li
Journal: Journal of Clinical Oncology (2022)

4103 Background: Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide, especially in Asian counties. Patients can be treated more effectively if detected earlier, however the current screening strategies with alpha-fetoprotein (AFP) or ultrasound it is largely suboptimal. We aimed to develop non-invasive and cost-effective assay to improve HCC early detection. Methods: HCC-specific DNA methylation markers were screened from tissue and plasma samples through a modified reduce representation bisulfite sequencing assaay,and optimized by a targeted methylation sequencing assay. The most informative markers were then integrated in a multi-locus qPCR assay, HepaQ. Results: Profiling DNA methylation pattern on 61 tissue samples (31 HCC tumor and 30 normal tissues) and 663 plasma samples (276 HCC and 393 control plasma samples) achieved an AUC of 0.99, which corresponds to 91% sensitivity at 94% specificity. The best-performance markers were further screened and analytically verified in additional tissues and plasmas after several rounds of marker selection. A multi-locus qPCR assay, designated as HepaQ, was then developed to incorporate the most effective markers. A cohort of 559 plasma samples including 293 HCC (84% of them at stage 0/A), 60 liver cirrhosis (LC), 36 chronic hepatitis B (CHB) and 170 healthy controls (CTRL), were used to train a classifier for HCC early detection. HepaQ classifier enables to detect 85.3% of HCC under a specificity of 88.3%, 91.7% and 92.4% in LC, CHB and CTRL, respectively. Finally, HepaQ classifier was validated in 374 plasma samples independently collected from multiple clinical centers to confirm its performance of 87.2% sensitivity in HCC and 86.8%,90.5% and 93.4% specificities in LC, CHB and CTRL respectively. Conclusions: We have developed and demonstrated a blood-based ctDNA methylation assay, HepaQ, that can detect early-stage HCC at high sensitivity and specificity. We proposed that HepaQ assay, a cost-effective qPCR assay, has the great potential to benefit the population at-risk for HCC early detection and screening.
Prevalence and clinical significance of pathogenic germline mutations in homologous recombination repair genes in Chinese lung cancer patients.
Authors: Yanxia Jiang, Liying Han, Yan Wang, Nuoting Wu, Suo Peisu, Tanxiao Huang
Journal: Journal of Clinical Oncology (2022)

e20547 Background: There is accumulating evidence indicating that pathogenic germline mutations may contribute to lung cancer susceptibility besides environmental factors. The prevalence and clinical significance of pathogenic germline mutations in homologous recombination repair genes on lung cancer susceptibility has not been systematically investigated. Methods: We used real-world HaploX genomic data from patients (pts) with lung cancer to determine the prevalence of pathogenic germline mutations in homologous recombination repair genes from July 2020 to January 2022. Results: Out of the 766 patients screened, 5.5% (42/766) of the patients harbored the pathogenic germline mutations：12 with ATM, 12 with FANCA, 8 with ATR, 7 with BRCA1, and 3 with BRCA2. Conclusions: A proportion of 5.5% of patients carrying germline mutations in homologous recombination repair genes may be potentially linked to increased susceptibility to lung cancer. Our study has demonstrated that pathogenic germline mutations in homologous recombination repair genes are a risk factor for lung cancer.
Safety results of Q-1802, a Claudin18.2/PD-L1 bsABs, in patients with relapsed or refractory solid tumors in a phase 1 study.
Authors: Jifang Gong, Lin Shen, Jie Hou, Xiaohua Chen, Qin Yu, Ying Zheng, Yakun Wang, Jian Zhang, Xiangdong Qu, Qiying Lu, Yejie Du, Qin Pan, Wencheng Xu
Journal: Journal of Clinical Oncology (2022)

2568 Background: Q-1802 is a humanized bispecific antibody that targets both the tumor -specific antigen CLDN18.2 and the immune checkpoint PD-L1. Methods: This is a first-in-human, phase 1a/1b, multicenter, dose escalation and dose expansion study of Q-1802 administered intravenously to adult pts with resistant/refractory advanced or metastatic solid tumors who had failed standard therapies. Monotherapy of Q-1802 was conducted in 20-30 enrolled subjects. In the dose escalation phase (phase 1a), an accelerated titration followed by a 3+3 design was used to assess the safety and tolerability of Q-1802 monotherapy (dose range 0.1 mg/kg to 20 mg/kg); and determine the maximum tolerated dose (MTD). Q-1802 was administered Q3w on a 21-day treatment cycle and dose limiting toxicity (DLT) observation period. Tumor assessments per RECIST v1.1 were performed once every 6 weeks (2 cycles). Q-1802 PK and PD analyses were performed. Results: As of Jan 20, 2022, a total of 9 patients (median age 57y; most patients received ≥3 prior regimens) were enrolled in phase 1a with DLT evaluation of the 20 mg/kg cohort currently in progress. The most common tumor types were GI cancers. There were no DLTs up to 10 mg/kg of Q-1802, inclusive. Phase 1a with DLT evaluation of the 20 mg/kg cohort currently in progress. The most common treatment related adverse events (TRAEs) were Gastrointestinal AE (66.7%, 6/9), including nausea 6/9 (66.7%), vomiting 5/9 (55.6%), abdominal pain 2/9 (22.2%) and diarrhea 2/9 (22.2%). The second common TRAEs were IRR (infusion related reaction) (33.3%, 3/9), including Fatigue 3/9 (33.3%), Fever 2/9 (22.2%), Chill 2/9 (22.2%), face pain 1/9 (11.1%). There was G1/2 except for one patient experienced a G3 skin rash, and one patient reported with a G3 Gastrointestinal AE. Two SAEs (G2 fever and G3 Gastrointestinal AE) were reported, both were considered as possibly related to study drug, but recovered shortly. No death reported due to study related treatment. Safety evaluation of the 20 mg/kg dose level is in progress. One Gastric cancer patient (moderate CLDN18.2 expression at baseline) with prior heavily treatment observed clinical benefit and response with Non-CR/Non-PD at first tumor assessment at dose of 10mg/kg and continues the therapy. Q-1802 drug exposure increased with increasing dose. The elimination of Q-1802 appears to follow first-order elimination kinetics. Conclusions: Q-1802 bsABs has presented safe and well-tolerated profile up to doses of 10 mg/kg. The dose escalation is still in progress. Clinical trial information: NCT04856150.
Efficacy proof-of-concept from a phase 1 study of a novel therapeutic peptide, ST101, targeting the oncogenic transcription factor C/EBPβ in patients with refractory solid tumors.
Authors: T.R. Jeffry Evans, Nehal J. Lakhani, Hendrik-Tobias Arkenau, Meredith McKean, Stefan N. Symeonides, Fabio Massaiti Iwamoto, Jim Rotolo, Gina Capiaux, Rob Michel, Stephen Kaesshaefer, Alice Susannah Bexon, Gerald Steven Falchook
Journal: Journal of Clinical Oncology (2022)

3014 Background: The oncogenic transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) promotes tumor survival and proliferation and inhibits differentiation. ST101 is a peptide antagonist of C/EBPβ, with anti-tumor activity in prostate cancer (PC), glioblastoma (GBM), breast cancer (BC), melanoma, and other pre-clinical models. Methods: This phase 1 study enrolled patients (pts) with refractory solid tumors with varying histologies. The primary objective was to evaluate safety/tolerability of ST101 and to determine the recommended phase 2 dose (RP2D). Secondary and exploratory objectives included pharmacokinetics (PK), preliminary efficacy (RECIST 1.1), and pharmacodynamic (PD) evaluation. The study used a 3+3 dose-escalation design, with once-weekly IV infusion dosing of ST101 at 0.5, 1, 2, 4, 6, 9 mg/kg or a flat dose of 500 mg. Results: Enrollment in phase 1 was completed in November 2021 with a total of 25 pts with multi-metastatic disease that were refractory to standard therapy. As of February 15, 2022, five pts remain on study with a median treatment duration of 27 weeks’ (16-77). There were no DLTs, dose modifications, or serious adverse events (SAEs) related to ST101. The only AEs of note were G1-2 histaminergic infusion-related reactions (IRRs), largely pruritis and urticaria, managed with antihistamines, montelukast, and interruption/slowing of infusion. IRRs affected 93% of pts on the first dose at ≥4mg/kg and led to prolongation of infusion time. Intensity and frequency of IRRs decrease with repeat dosing. No other AEs were consistently reported. There was no evidence of accumulation upon continued exposure of ST101 and no anti-drug antibodies. Tumor immunohistochemistry showed dose-proportionate staining for ST101 and decreased tumor proliferation in several pts represented by decreased Ki67 expression. Population PK analysis supported flat dosing in phase 2. Five pts continue on treatment with one confirmed partial response in a patient with cutaneous melanoma lasting &gt;42 weeks and four pts with ongoing stable disease. Conclusions: ST101 demonstrated safety at all doses explored and evidence of efficacy across dose levels, particularly higher doses and in pts with melanoma. PK and PD support a dose relationship for efficacy and selection of 500 mg as the RP2D. Pts are now enrolling in phase 2 cohorts to assess response in cutaneous melanoma, GBM, castrate-resistant PC, and HR + BC. Clinical trial information: NCT04478279. [Table: see text]
Can an artificial intelligence-based platform reduce physician burden and increase access to clinical trials?
Authors: Limor Gortzak Uzan, J. Leonard Leonard Lichtenfeld, Tzvia Bader, Avital Gaziel
Journal: Journal of Clinical Oncology (2022)

1552 Background: Clinical trials for cancer patients are an important treatment option and a resource for drug development. Although patients are more actively searching for treatment options through various approaches, the national average of cancer patients accrued to clinical trials remains static at only 2-4%. The most widely recognized resource is clinicaltrials.gov, which does not offer direct trial matching, is geared toward healthcare professionals and uses complex medical terms that are challenging for many patients. For clinicians, the absence of real-time access and insight into all relevant oncology trials, forms a burden on their already-limited time. Alleviating this burden could reduce barriers to clinical trial accrual. Methods: Using AI and an unsupervised natural language process approach, the Trialjectory platform monitors, analyzes and matches patients to clinical trials. Matching is achieved by patient response to a dynamic set of questions curated based on the eligibility criteria of available trials. The online questionnaire (www.trialjectory.com) collects detailed clinical data that include disease characteristics (histological, molecular and mutational status), treatment history, general health and comorbidities. All collected data points are incorporated into the matching process, yielding a high-quality actionable matched-trial list. A skilled support team is available to answer questions and concerns via email, text or phone calls. The platform enables patients to share the matched trial list with their oncologist for discussion. Results: from July 2019 - December 2021, 49,906 cancer patients completed Trialjectory’s questionnaire. Patient accrual grew rapidly since the second half of 2019 with 1462, 2201, 9364,12685, and 24194 new questionnaire completions in each consecutive 6-month period from the 2nd half of 2019 through December 2021. 49,199 (98.6%) of registered patients were found eligible for available trials. Of the matched patients, 4428 patients (9%) applied to a clinical trial. Our matching engine identifies each specific trial match to each patient profile with a sensitivity of 90% and a specificity of 95%. When aggregated to a patient level, the chance that a patient will be matched for at least one trial from those that he is eligible to is 99.9%. Metrics are validated by automatically matching multiple artificially-created patient profiles and manually verifying the quality of the match. Conclusions: TrialJectory is an effective AI-based tool that offers cancer patients and their oncologists direct, precise and quick access to relevant clinical trials. Our data show a high adoption and growing registration rates and well-above average clinical trial application rate. By democratizing the access to clinical trials, increased opportunities are noted that might lead to increased trial participation.